Abstract Background Chronic postsurgical pain (CPSP) affects between 7-23% and 13-44% of patients after hip and knee arthroplasty, respectively. Standardised methods of pain assessment provide superior evaluation of pain, including the Oxford Joint Score Pain Subscale (OJS-PS). We aim to estimate the proportion of patients with a phenotype consistent with CPSP through a k-medoids clustering technique and identify a threshold on the OJS-PS to highlight such patients at a population level. Methods In this cross-sectional study Patient Reported Outcomes Measures data 6-months after hip and knee arthroplasty from 2017 to 2025 were examined. An adapted k -medoid clustering technique utilising subsampling, batch assignment and probabilistic consensus allocated clusters. A receiver operator characteristic analysis identified a threshold on the OJS-PS noting the lowest scoring cluster. Our categorisation was compared to self-reported severe or moderate pain; sensitivity, specificity and accuracy of this categorisation were calculated. Results We analysed 109,542 hip and 113,799 knee arthroplasty patients; three clusters were used in each analysis. After hip arthroplasty: 14.4% of patients were assigned to the cluster with the lowest median OJS-PS of 11 [IQR 8 – 13]. A threshold of 15.5 classified patients as severe or moderate pain with 60.6% sensitivity, 91.0% specificity and 85.7% accuracy. Similarly, after knee arthroplasty, 25.3% were assigned to the cluster with the lowest median OJS-PS of 14 [IQR 11 – 16]. A threshold of 18.5 on the OJS-PS had an 85.4% sensitivity, 88.4% specificity and 87.8% accuracy for classifying patients with self-reported severe or moderate pain. Conclusions This robust and scalable clustering technique on ordinal clinical data estimates the proportion of patients reporting a phenotype consistent with CPSP. On a population level the thresholds identified on the OJS-PS could aid screening for potential CPSP patients 6 months after hip and knee arthroplasties.

BACKGROUND:Chronic non-malignant pain (CNMP) is common in low- and middle-income countries (LMICs), yet access to potent opioids is often constrained by fears of misuse and diversion. In Pakistan, community pharmacists (CPs) have no patient-oriented opioid optimisation services despite specialised roles in medicines optimisation in high-income settings. OBJECTIVE:This study aimed to explore and identify barriers, facilitators, and strategies for developing and implementing a novel opioid optimisation service for CNMP in Pakistan. METHODS:A mixed-methods study was conducted in Pakistan from November 2019 to December 2020. Qualitative data were collected through six case studies , semi-structured interviews with pharmacy policymakers (n = 11) and individuals with CNMP (n = 14), and focus groups with doctors (n = 31) and CPs (n = 36). Data were inductively analysed using reflexive thematic analysis supported by NVivo 12, and case study observations in six community pharmacies were examined using cross-case synthesis with an explanation-building approach. Findings were deductively mapped to an adapted implementation science framework (LMIC-CFIR and FISpH), and an implementation research logic model was developed to theorize how implementation strategies might operate through underlying mechanisms to support service delivery and implementation. RESULTS:Barriers and corresponding strategies were identified across five domains (intervention, system, community, organisation, individual). strategies included CP remuneration, regulatory reform and policymaker support, public awareness initiatives, organisational support in community pharmacies, and enhancement of CP knowledge, skills, and motivation. CONCLUSIONS:The study outlines strategies to address multilevel barriers to implementing a novel opioid optimisation service and proposes a pathway for policymakers to mobilise the community pharmacy workforce to optimise opioid use among people with CNMP in Pakistan.

Abstract Bullous pemphigoid (BP) is a rare, autoimmune blistering skin disease primarily affecting older adults. Recent evidence suggests an association between antibiotics and BP risk. This study focused on assessing a dose–response association. A population-based nested case–control study was conducted using the Clinical Practice Research Datalink Aurum (1998–2021). Adults with an incident BP diagnosis were matched with up to five controls by age, sex and general practice. Antibiotic prescriptions within 6–12 months before diagnosis were considered, excluding the preceding 6 months to reduce protopathic bias. Exposures (by group, classes, subclasses and substances) included the number of prescriptions, cumulative number of defined daily doses (cDDDs), cumulative durations (days) and time since last prescription (days). Reference groups were people not exposed to specific antibiotics. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated using multivariable conditional logistic regression, accounting for confounders. There were 11 156 cases and 52 201 controls. Most antibiotics (except clarithromycin and oxytetracycline) showed dose–response associations with BP risk, peaking 6–8 months after exposure. Strong associations (aOR > 2, P < 0.001) were observed for flucloxacillin and trimethoprim. For flucloxacillin, the aOR increased from 2.22 (95% CI 1.96–2.50) for one prescription to 3.44 (2.80–4.23) for at least two prescriptions, consistent with cDDDs ≤ 7 (2.28, 2.02–2.57), > 7–14 (3.26, 2.54–4.19) and > 14 (2.97, 2.11–4.19); and cumulative durations ≤ 7 (2.14, 1.89–2.43), > 7–14 (3.56, 2.84–4.46) and > 14 (3.13, 2.28–4.30). BP risk remained elevated throughout 1 year after the last flucloxacillin prescription (aOR 1.97, 95% CI 1.60–2.43). Trimethoprim also showed elevated risk with at least two prescriptions (aOR 1.98, 95% CI 1.58–2.49), and higher risk for > 7–14 cDDDs (2.25, 1.65–3.06) and cumulative durations > 7–14 (2.00, 1.47–2.73) and > 14 (2.03, 1.50–2.75). These findings highlight the need for mindful antibiotic prescribing, especially repeated or prolonged courses, in people at risk of BP, while acknowledging confounding by indication as a limitation.

Background Opioids offer limited long-term benefits and carry significant risks. We developed the PROMPPT intervention to address challenges in implementing effective person-centred review and safe opioid tapering in UK primary care. PROMPPT comprises a primary care review, led by clinical pharmacists working in general practices as part of the multidisciplinary team, and an associated training package. This trial will evaluate (1) the effectiveness of PROMPPT in supporting people with persistent non-cancer pain to safely reduce opioids, where appropriate, without increasing pain/pain-related interference, and (2) cost-effectiveness compared with usual primary care. Methods Design and setting: cluster randomised controlled trial, with internal pilot, in 38 general practices across England. Participants: patients ≥18 years prescribed one or more opioids ≥6 months for persistent pain who consent to participate in a questionnaire study. Exclusions: acute pain, cancer pain, end-of-life care, dementia, severe mental illness or otherwise vulnerable, and current substance misuse treatment. Practices are randomly allocated (1:1) to either: invite participants for a PROMPPT review with a trained practice pharmacist, and follow-up as needed, or continue usual primary care review for patients who are prescribed opioids. Co-primary outcomes, measured at 12 months, are (1) reduction in self-reported opioid use (≥25% reduction in daily morphine equivalent dose from their baseline) and (2) non-inferiority of the Brief Pain Inventory total score. The trial includes an economic evaluation (within trial and longer-term cost-utility analyses) and a mixed methods process evaluation. Analysis of consultation audio-recordings, case report forms (including an intervention delivery template), acceptability questionnaires and semi-structured interviews will explore how PROMPPT was delivered and received, and how context affected implementation and outcomes. Conclusion The PROMPPT trial will assess whether review by trained clinical pharmacists working in general practices can support safe opioid reduction without compromising pain management and quality of life. Trial registration ISRCTN 45616481, 13/05/2022 https://doi.org/10.1186/ISRCTN45616481

Background Often, people living with persistent non-cancer pain are prescribed opioids long term, despite a lack of evidence for their long-term effectiveness and safety. This study informed the design of a new practice pharmacist-led review (the PROMPPT review) for people prescribed opioids for persistent pain in UK primary care. Aim To explore the perspectives of pharmacists working in UK general practice regarding the proposed PROMPPT review, and to identify barriers to and facilitators of its delivery in practice, including supporting opioid deprescribing where appropriate. Design & setting Multi-method qualitative study conducted with pharmacists working in primary care, who were recruited via professional networks predominantly in the East Midlands and West Midlands, UK. Method Pharmacists with experience of consulting in primary care participated in semi-structured interviews ( n = 13) and two focus groups ( n = 16) to explore attitudes to, beliefs about, and experiences of the proposed PROMPPT review for people living with persistent pain. The Theoretical Domains Framework (TDF) provided a framework for data collection and thematic analysis. Facilitators and barriers were mapped to components of the Capability Opportunity Motivation — Behaviour (COM-B) model. Results In total, 16 facilitators and barriers relating to the delivery of the PROMPPT review were identified across 10 domains of the TDF. Factors included access to evidence-based patient-facing resources, receiving professional colleagues’ peer support, and having a therapeutic alliance with patients. These mapped to the COM-B model components as follows: capability (knowledge, skills), opportunity (environmental context and resources, social influences), and motivation (social or professional role and identity, beliefs about capabilities, beliefs about consequences, intentions, goals, emotions). Conclusion This study provides theoretically based evidence of factors influencing pharmacists’ delivery of the proposed PROMPPT review in relation to pharmacist capability, motivation, and opportunity. This work informed the co-design of both the intervention and the pharmacist training package.

Given the poor long-term effectiveness of opioids for persistent non-cancer pain, and their potential for harm, evidence-based interventions to address opioid overprescribing for persistent pain are needed. This study aimed to explore the acceptability and feasibility of a primary care practice pharmacist-led intervention (PROMPPT review) for patients prescribed opioids for persistent pain and the feasibility of evaluating PROMPPT in a definitive trial. A single-arm study, with mixed methods process evaluation, was conducted in four English primary care practices. Adults prescribed opioids for ≥ 6 months were invited to participate in the Management of Opioids and Persistent Pain (MOPP) study by completing baseline and 3-month follow-up questionnaires. Practices invited a representative sample of MOPP participants to schedule a PROMPPT review, eight of which were audio-recorded. Following the review, pharmacists completed intervention delivery templates, and participants were sent an Acceptability Questionnaire and invited to consent to an interview. Between November 2020 and May 2021, 148 participants were recruited to the MOPP study. Of these, 123 (83 ISRCTN87628403 , registered 31 July 2020

The personal, social and economic burden of chronic pain is enormous. Tremendous research efforts are being directed toward understanding, preventing, and managing chronic pain. Yet patients with chronic pain, clinicians and the public are sometimes poorly served by an evidence architecture that contains multiple structural weaknesses. These include incomplete research governance, a lack of diversity and inclusivity, inadequate stakeholder engagement, poor methodological rigour and incomplete reporting, a lack of data accessibility and transparency, and a failure to communicate findings with appropriate balance. These issues span pre-clinical research, clinical trials and systematic reviews and impact the development of clinical guidance and practice. Research misconduct and inauthentic data present a further critical risk. Combined, they increase uncertainty in this highly challenging area of study and practice, drive the provision of low value care, increase costs and impede the discovery of more effective solutions.In this focus article, we explore how we can increase trust in pain science, by examining critical challenges using contemporary examples, and describe a novel integrated conceptual framework for enhancing the trustworthiness of pain science. We end with a call for collective action to address this critical issue. Perspective Multiple challenges can adversely impact the trustworthiness of pain research and health research more broadly. We present ENTRUST-PE, a novel, integrated framework for more trustworthy pain research with recommendations for all stakeholders in the research ecosystem, and make a call to action to the pain research community.

BACKGROUND:Stakeholder involvement is a core element of the Medical Research Council (MRC) framework for developing and evaluating complex interventions, but approaches to involve stakeholders are not well-reported. We outline how stakeholders contributed to co-designing a Proactive clinical Review of patients taking Opioid Medicines long-term for persistent Pain led by Pharmacists working in primary care Teams (the PROMPPT intervention-a review and pharmacist training package). METHODS:We brought key stakeholders together to co-design the PROMPPT intervention using a person-based approach, alongside evidence from best practice guidance. We established a community of practice comprising three complementary groups: a patient advisory group, a pharmacist advisory group and a mixed stakeholder group. Patient stakeholders were identified from an existing patient involvement group. Professional stakeholders were identified using networks and social media. The three groups met in iterative workshops with predefined aims. We offered reimbursement for the stakeholders' time. OUTCOMES:The patient advisory group (n = 10), pharmacist advisory group (n = 6) and mixed stakeholder group (n = 16) each met for 2 or 3 workshops between April 2019 and February 2020. Stakeholders had expertise, often cross-cutting, in lived experience, persistent pain, opioids, delivering primary healthcare and/or promoting behaviour change. Patient stakeholders provided their perspectives of consulting about their pain and opioids. Pharmacist stakeholders provided their perspectives on how pain reviews were happening in practice and on considerations for training (e.g., vignettes and experiential learning were considered important). The mixed stakeholder group provided a breadth of views highlighting current practice, including the value of engaging the wider GP practice team, issues around clinical responsibility for prescribing and the fact that international clinical guidance was not always relevant to UK primary care. CONCLUSIONS:By understanding the context of the PROMPPT intervention, stakeholders worked to develop a new pharmacist-led primary care review ahead of feasibility testing. We make recommendations for future developers of complex interventions. PATIENT AND PUBLIC CONTRIBUTION:Patient stakeholders, including a lay co-applicant (C.S.) supported by a PPI support worker (A.H.), helped develop and refine the intervention. C.S. and A.H. read and contributed to the initial manuscript and approved the final manuscript.

Introduction Long term use of benzodiazepines and z-drugs is associated with dependence and withdrawal, forming a significant component in the Public Health England report focussing on dependence and withdrawal from prescribed medicines [1]. Despite a national reduction in benzodiazepine and z-drug prescribing between 2015 and 2020, Boston Primary Care Network (PCN) hypnotic prescribing rates remained relatively constant and significantly above the national average [2]. In 2020 Boston PCN employed their first Clinical Pharmacists to focus on the NHS England Medicines Optimisation priorities, including dependence forming medicines [3]. PCN Pharmacist led clinics were established to provide patient-centred holistic support to patients taking long-term hypnotics.Introduction Long term use of benzodiazepines and z-drugs is associated with dependence and withdrawal, forming a significant component in the Public Health England report focussing on dependence and withdrawal from prescribed medicines [1]. Despite a national reduction in benzodiazepine and z-drug prescribing between 2015 and 2020, Boston Primary Care Network (PCN) hypnotic prescribing rates remained relatively constant and significantly above the national average [2]. In 2020 Boston PCN employed their first Clinical Pharmacists to focus on the NHS England Medicines Optimisation priorities, including dependence forming medicines [3]. PCN Pharmacist led clinics were established to provide patient-centred holistic support to patients taking long-term hypnotics.Introduction Long term use of benzodiazepines and z-drugs is associated with dependence and withdrawal, forming a significant component in the Public Health England report focussing on dependence and withdrawal from prescribed medicines [1]. Despite a national reduction in benzodiazepine and z-drug prescribing between 2015 and 2020, Boston Primary Care Network (PCN) hypnotic prescribing rates remained relatively constant and significantly above the national average [2]. In 2020 Boston PCN employed their first Clinical Pharmacists to focus on the NHS England Medicines Optimisation priorities, including dependence forming medicines [3]. PCN Pharmacist led clinics were established to provide patient-centred holistic support to patients taking long-term hypnotics.Aim This review aimed to evaluate a Pharmacist-led service for patients prescribed long-term hypnotics (benzodiazepines and Z-drugs).Methodology Patients who were taking a benzodiazepine or z-drug for chronic insomnia for longer than six consecutive months between April 2020 and April 2025 were included. Those taking benzodiazepines for alternative indications such as anxiety were excluded (those with chronic insomnia and concurrent indications for benzodiazepines were included in the review). Data was collected using electronic patient records and analysis was completed using Microsoft Excel. Confidential patient data was anonymised prior to analysis therefore no ethical approval was required.Methodology Patients who were taking a benzodiazepine or z-drug for chronic insomnia for longer than six consecutive months between April 2020 and April 2025 were included. Those taking benzodiazepines for alternative indications such as anxiety were excluded (those with chronic insomnia and concurrent indications for benzodiazepines were included in the review). Data was collected using electronic patient records and analysis was completed using Microsoft Excel. Confidential patient data was anonymised prior to analysis therefore no ethical approval was required. Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Results 91 patients reviewed in Pharmacist-led clinics were retrospectively evaluated over a five-year period between April 2020 to April 2025. Pharmacist impact - deprescribing Over the five-year period, 47 out of 91 patients (52%) discontinued their hypnotic medication. A further 32 patients (35%) achieved a partial reduction in their hypnotic daily dosing. The median time taken to deprescribe hypnotic medication was 18 months (interquartile range (IQR) 18.5 months). Drug, dosing and duration Patients prescribed temazepam and zolpidem had a higher discontinuation rate versus zopiclone. Temazepam was discontinued in 5 out of 7 patients (71%) and zolpidem was discontinued in 9 out of 13 patients (69%), whereas zopiclone was discontinued in 33 out of 71 patients (47%). Patients prescribed temazepam achieved the highest average (mean) daily dose reduction (89%) vs. zolpidem (82%) and zopiclone (69%). For those who reduced and stopped their hypnotic medication, the median duration of hypnotic prescribing prior to Pharmacist intervention was 10 years (IQR 10.5 years), compared to a median of 7.5 years (IQR 9.25 years) for those patients where no dose reduction was possible. Holistic management - signposting and referrals 43 out of 91 patients (47%) were referred to wider multidisciplinary (MDT) services including psychological therapy (26/91 = 29%), specialist mental health services (12/91 = 13%) and social prescribers (4/91 = 4%). 19 of the 43 (44%) patients referred managed to wean and stop hypnotic medication over the five-year period.Discussion There was a high success rate in deprescribing and daily dose reduction. Existing national guidance for long-term hypnotic withdrawal recommends a gradual reduction over a 16-to-20-week period [4]. This retrospective analysis of Pharmacist-led intervention demonstrates that a more gradual weaning process is often necessary and highly effective. Deprescribing of temazepam and zolpidem was far more successful in comparison to zopiclone, however the smaller sample size for temazepam (n = 7) and zolpidem (n = 13) in comparison to zopiclone (n = 73) limits the ability to draw definitive conclusions. Analysis of referrals to and engagement with support across the multidisciplinary team suggests patients with complex needs were more frequently offered holistic support including psychological therapy, specialist mental health services and social prescribers. This complexity may explain the reduced frequency of success of deprescribing in this patient group.Discussion There was a high success rate in deprescribing and daily dose reduction. Existing national guidance for long-term hypnotic withdrawal recommends a gradual reduction over a 16-to-20-week period [4]. This retrospective analysis of Pharmacist-led intervention demonstrates that a more gradual weaning process is often necessary and highly effective. Deprescribing of temazepam and zolpidem was far more successful in comparison to zopiclone, however the smaller sample size for temazepam (n = 7) and zolpidem (n = 13) in comparison to zopiclone (n = 73) limits the ability to draw definitive conclusions. Analysis of referrals to and engagement with support across the multidisciplinary team suggests patients with complex needs were more frequently offered holistic support including psychological therapy, specialist mental health services and social prescribers. This complexity may explain the reduced frequency of success of deprescribing in this patient group.Discussion There was a high success rate in deprescribing and daily dose reduction. Existing national guidance for long-term hypnotic withdrawal recommends a gradual reduction over a 16-to-20-week period [4]. This retrospective analysis of Pharmacist-led intervention demonstrates that a more gradual weaning process is often necessary and highly effective. Deprescribing of temazepam and zolpidem was far more successful in comparison to zopiclone, however the smaller sample size for temazepam (n = 7) and zolpidem (n = 13) in comparison to zopiclone (n = 73) limits the ability to draw definitive conclusions. Analysis of referrals to and engagement with support across the multidisciplinary team suggests patients with complex needs were more frequently offered holistic support including psychological therapy, specialist mental health services and social prescribers. This complexity may explain the reduced frequency of success of deprescribing in this patient group.

BACKGROUND:Bullous pemphigoid (BP) is an autoimmune skin disease that mainly affects older people. Based on case series and small hospital-based studies, a number of drugs have been associated with BP. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of any potential increased risk of BP following the administration of certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved wellbeing. OBJECTIVES:To determine the association between drugs/vaccines commonly prescribed to older people and the risk of developing BP. METHODS:We conducted a population-based nested case-control study between 1998 and 2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched patients with BP with up to five controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, in a sensitivity analysis, we considered that drugs may be prescribed for undiagnosed symptoms of BP that resemble skin infection (protopathic bias). RESULTS:Antibiotics were associated with the highest risk of BP [odds ratio (OR) 4.60, 95% confidence interval (CI) 4.40-4.80]. However, after adjusting for protopathic bias, the OR decreased to 2.08 (95% CI 1.99-2.17). Also, after adjusting for protopathic bias, of all the antibiotic classes and subclasses, penicillins [OR 3.44, 95% CI 3.29-3.60 (sensitivity analysis OR 1.74, 95% CI 1.66-1.84)] and penicillinase-resistant penicillins [OR 7.56, 95% CI 7.15-8.00 (sensitivity analysis OR 2.64, 95% CI 2.45-2.85)] had the strongest associations with BP risk. Other drugs strongly associated with increased risk were gliptins (OR 2.77, 95% CI 2.37-3.23) and second-generation antipsychotics (OR 2.58, 95% CI 2.20-3.03). CONCLUSIONS:Healthcare professionals need to be aware of BP risk in older people, particularly when prescribing penicillinase-resistant penicillins, gliptins and second-generation antipsychotic drugs, to recognize and manage BP early. Owing to the low disease prevalence, we do not suggest avoiding certain drugs/vaccines to prevent BP. Further research should consider recency, dosage and duration of antibiotic treatments.

The ENTRUST-PE project convened an international, interdisciplinary network to develop an integrated framework for enhancing and facilitating the trustworthiness of pain research. This summary outlines the key features of that framework and presents recommendations for Regulators and Policymakers.

Objective The present study explored fall recording in primary care data and in primary- secondary care linked data, to inform the data source adequacy for examining the association between analgesic use and the risk of falls in patients with knee osteoarthritis (KOA). Method Data were obtained from the clinical practice research datalink (CPRD) and Hospital Episode Statistics (HES). The study population included adults with an incident diagnosis of KOA recorded in CPRD between 2000 and 2014. The study captured the proportion of fallers in CPRD, HES or both and measured the gap between fall recording in both databases. Descriptive statistics were used report study measures Results There were 104,082 patients diagnosed with KOA in CPRD standalone data; 3,275 (3.1%) of them had a fall while HES-linked data included 57,383 and 2,384 (4.1%) of them had a fall recorded within one year of KOA diagnosis. Among the linked population, 1,852 (3.2%) had a fall record only in CPRD; however, there were an additional 365 (0.6%) patients who had a fall recorded only within HES data, while167 (0.3%) patients had it recorded in both databases. There was a median of 19.5 days’ difference (IQR 4.5, 91) in fall recording between primary and secondary care data. Conclusion CPRD records included 84.7% of the overall falls experienced by patients within one year of their KOA diagnosis. However, 15.3% of the falls were only recorded in hospital data; although not a substantial proportion, this represents a group that probably suffered a serious event.

The ENTRUST-PE project convened an international, interdisciplinary network to develop an integrated framework for enhancing and facilitating the trustworthiness of pain research. This summary outlines the key features of that framework and presents recommendations for Institutions that undertake research.

BACKGROUND:Electronic health records (EHR) are frequently used for epidemiological research including drug utilisation studies in a defined population such as the population with knee osteoarthritis (KOA). We sought to describe the process of defining a cohort of patients with KOA from a large UK primary care database and estimate the annual incidence of diagnosed KOA between 2000 and 2015. METHOD:This was a retrospective study using data from the clinical practice research datalink (CPRD). CPRD is a large primary care longitudinal electronic medical records' database that contains anonymous records of patients from general practices across United Kingdom. Five different cohort definition strategies were applied including symptoms-based or diagnosis-based strategies or a combination of both. To validate results, the annual incidence of KOA was estimated and compared to published data. RESULTS:The study defined 898,690 patients when symptoms-based strategy was applied, 137,541 patients when diagnosis based and 83,294 when a combination of both strategies were applied. The final cohort was defined using a diagnosis-based strategy that avoided overestimation (with symptoms-based definition) or underestimation (with a combination of symptoms and diagnosis). The incidence of KOA ranged from 1.33 per 1000 CPRD registrants in 2000, 1.76 in 2008 and 1.45 patients in 2015. CONCLUSION:This study logically/sensibly defined a cohort of patients with diagnosed KOA through the application of several strategies. This was an essential step to avoid subsequent over or underestimation of the prevalence of drug utilisation and the associated adverse clinical outcomes within primary care patients with KAO.

The ENTRUST-PE project convened an international, interdisciplinary network to develop an integrated framework for enhancing and facilitating the trustworthiness of pain research. This summary outlines the key features of that framework and presents recommendations for Peer Reviewers of research.

Pharmacological pain treatment in older persons is presented by a multi-disciplinary group of European pain experts. Drugs recommended for acute or chronic nociceptive pain, also for neuropathic pain and the routes of administration of choice are the same as those prescribed for younger persons but comorbidities and polypharmacy in older persons increase the risk of adverse effects and drug interactions. Not all drugs are available or authorised in all European countries. For mild-to-moderate pain, non-opioids including paracetamol and non-steroidal anti-inflammatory drugs are first-line treatments, followed by nefopam and metamizole. Codeine, dihydrocodeine and tramadol are prescribed for moderate to severe pain and ‘strong’ opioids, including morphine, hydromorphone, oxycodone, fentanyl, buprenorphine, methadone and tapentadol, for severe pain. Chronic neuropathic pain treatment relies on coanalgesics, including anti-epileptics (gabapentinoids) and anti-depressants with additional option of topical lidocaine and capsaicine. The choice of analgesic(s) and the route of administration should be guided by the pain characteristics, as well as by the patient’s comorbidities, organ function and medications. Several directions have been highlighted to optimise pharmacological pain management in older individuals: (1) before starting pain treatment adequately detect and assess pain and always perform a full geriatric assessment, (2) consider kidney function systematically to adjust the doses of analgesics and avoid the risks of overdose, (3) start with the lowest dose of an analgesic and increase it gradually under the control of the effect, (4) involve the older persons and family in their treatment, (5) reevaluate pain regularly during treatment and (6) combine pharmacological treatment with non-pharmacological approaches.